It is the broad goal of this project to investigate the physiology of GnRH deficient male by using GnRH deficient males undergoing long-term administration of GnRH for induction of sexual maturation and normal men. By contrasting their responses to a variety of modulatory influences known to impact upon the hypothalamic- pituitary-gonadal-axis of the male, we will attempt to determine the site of action and relative contribution of testosterone and estradiol feedback upon the hypothalamic-pituitary-axis in the male. In addition, we will determine the role of physiologic variations in the interpulse interval and contour of the GnRH pulse upon the quantitative and qualitative nature of gonadotropin secretion in the male. Finally, we will measure inhibin levels by radioimmunoassay in GnRH-deficient men during induction of sexual maturation with GnRH and in adult males. These levels will be correlated with gonadal size, the onset of spermatogenesis, and FSH secretion. With the combined use of normal males with an intact and free- running hypothalamic-pituitary-gonadal axis and GnRH deficient men in whom the hypothalamic input can be experimentally defined, it should be possible to provide new and useful information in the physiology of GnRH in the human. Such information is a critical step for the understanding and definition of abnormalities of the male reproductive system.